Immune function is significantly compromised after injury, and this condition can lead to increased susceptibility to infection, especially by opportunistic microorganisms. Infection, in turn, can progress to sepsis syndrome and shock which are significant causes of morbidity and mortality for the injured patient. Therefore, attenuation or prevention of injury associated immune dysfunction should diminish the incidence and severity of infection and its sequelae. Paramount to this approach is an understanding of the etiology and mechanisms of injury induced dysfunction. Using defined murine models of injury, the overall aim of this proposal is to identify the mediators that initiate the injury induced decline in macrophage activity and to determine the cellular and subcellular mechanisms responsible for subsequent macrophage dysfunction. Mechanisms of cellular dysfunction will be studied in resident peritoneal macrophages by: 1) assessing distal functions such as phagocytosis of opsonized beads, PMA 02 production, proinflammatory cytokine (TNF & IL-6) production, and processing and presentation of specific antigen; 2) characterizing defects in afferent signaling pathways; 3) assessing defects in efferent cytokine protein synthetic pathways and turnover; and 4) defining the role of glucocorticoids as mediators of injury induced macrophage dysfunction.